Factor Xlla protease inhibitors

Heparin has been found to bind a large number of proteins (Table 3). The biological activity of heparin and related polysaccharides is usually ascribed to their interaction with heparin-binding proteins. These proteins can be classified into classes including (1) enzymes, (2) protease inhibitors, (3) lipoproteins, (4) growth factors, (5) chemokines, (6) selectins, (7) extracellular matrix proteins, (8) receptor proteins, (9) viral coat proteins, (10) nuclear proteins, and (11) other proteins (1). Many heparin-binding proteins are enzymes and enzyme inhibitors. For example, proteases in the coagulation cascade, such as factors Ha, IXa, Xa, Xlla, and Villa, are heparin-... 

The cereal dual function a-amylase/trypsin inhibitor proteins are cysteine-rich, disulphide-rich, double-headed, 13-16 kDa, dual function inhibitor proteins that inhibit both of the digestion enzymes a-amylase and trypsin [290-325] (Table 11). Thus the Zea (com) member of this family, com Hageman factor inhibitor (CHFI), is a double-headed 14 kDa protein that inhibits a-amylase and the serine proteases trypsin and blood clotting Factor Xlla [323-324] (Table 11). The structures of the bifunctional a-amylase/trypsin inhibitor proteins from Eleusine (ragi) (RBI) [292-295] and Zea (com) (CHFI) [325] have been determined. These proteins are structurally similar to the lipid transfer proteins, being composed of a bundle of 4 a-helices together with a short [3-sheet element connected by loops, the a-amylase- and protease-inhibitory domains being separately located [325]. 

Antithrombin. A serine protease inhibitor (serpin) that degrades the serine proteases of thrombin, factors IXa, Xa, XIa and Xlla. It is constantly active, but its adhesion to these factors is increased by the presence of heparin sulphate (a glycosaminoglycan) or the administration of heparins (different heparinoids increase affinity to factor Xa, thrombin, or both). Deficiency of antithrombin (inborn or acquired, e.g. in proteinuria) leads to thrombophilia. 

Mechanism Heparin catalyzes the binding of antithrombin III (a serine protease inhibitor) to factors Ila, IXa, Xa, XIa, and Xlla, resulting in their rapid inactivation 4- Hepatic synthesis of vitamin K-dependent factors II, VII, IX, j X-—coumarins prevent 1 y-carboxylation by inhibiting vitamin K epoxide reductase no effect on factors already present. j In vivo effects only 1... 

Antithrombin (AT) is a serine protease inhibitor that inhibits thrombin, factor Xa, IXa, XIa, Xlla, tPA, urokinase, trypsin, plasmin, and kallikrein (Lahiri et al. 1976 Travis and Salvesen, 1983 Menache, 1991 Menache et al. 1992). Human Antithrombin of molecular weight equal approximately to 58,000 Da, contains 432 amino acids, three disulfide bridges, and four carbohydrate side chains, which account for 15% of the total mass (Magnusson, 1979 Franzen et al. 1980). Human antithrombin is synthesized in the liver and present in plasma at levels of 14 to 20mg/dl (Murano et al. 1980 Rosenberg et al. 1986). One cause of decreased level of antithrombin is pathological conditions. 

The mustard family (Brassicaceae) PIPs are 7 kDa proteins with 8 cysteines in highly conserved positions that form 4 disulphide linkages in a particular pattern of connectivity. The mustard PIPs are variously potent inhibitors of serine proteases such as trypsin, chymotrypsin, thrombin, plasmin and blood clotting factors Xa and Xlla [515, 520] (Table 15). 

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